Novel design of nickel cobalt boride nanosheets-decorated molybdenum disulfide hollow spheres as efficient battery-type materials of hybrid supercapacitors.

Transition metal borides (TMBs) with high theoretical capacitances and excellent electronic properties have attracted much attention as a promising active material of supercapacitors (SCs). However, TMB nanoparticles are prone to conduct self-aggregation, which significantly deteriorates the electrochemical performance and structural stability. To address the severe self-aggregation in TMBs and improve the active material utilization, it is imperative to provide a conductive substrate that promotes the dispersion of TMB during growths. In this work, sheet-like nickel cobalt boride (NCB) was grown on molybdenum disulfide (MoS2) hollow spheres (H-MoS2) by using simple template growth and chemical reduction methods. The resultant NCB/H-MoS2-50 was observed with uniform NCB nanosheets structure on the surface of the H-MoS2 and stronger MB bonding. After optimizing the loading amount of H-MoS2, the optimal composite (NCB/H-MoS2-50) modified nickel foam (NF) exhibits a superior specific capacity (1302 C/g) than that of the NCB electrode (957 C/g) at 1 A/g. Excellent rate capability of 84.8% (1104 C/g at 40 A/g) is also achieved by the NCB/H-MoS2-50 electrode. The extraordinary electrochemical performance of NCB/H-MoS2-50 is credited to the unique nanosheet-covered hollow spheres structure for facilitating ion diffusion and versatile charge storage mechanisms from the pseudocapacitive behavior of H-MoS2 and the Faradaic redox behavior of NCB. Furthermore, a hybrid SC is assembled with NCB/H-MoS2-50 and activated carbon (AC) electrodes (NCB/H-MoS2-50//AC), which operates in a potential window up to 1.7 V and delivers a high energy density of 76.8 W h kg-1 at a power density of 850 W kg-1. A distinguished cycling stability of 93.2% over 20,000 cycles is also obtained for NCB/H-MoS2-50//AC. These findings disclose the significant potential of NCB/H-MoS2-50 as a highly performed battery-type material of SCs.

Trace alcohol ether electrolytes with dual-site hydrogen bonds and modulated solvation structures for ultralong-life zinc-ion batteries.

Aqueous zinc-ion batteries (AZIBs) are highly regarded for their affordability, stability, safety, and eco-friendliness. Nevertheless, their practical application is hindered by severe side reactions and the formation of zinc (Zn) dendrites on the Zn metal anode surface. In this study, we employ tetrahydrofuran alcohol (THFA), an efficient and cost-effective alcohol ether electrolyte, to mitigate these issues and achieve ultralong-life AZIBs. Theoretical calculations and experimental findings demonstrate that THFA acts as both a hydrogen bonding donor and acceptor, effectively anchoring H2O molecules through dual-site hydrogen bonding. This mechanism restricts the activity of free water molecules. Moreover, the two oxygen (O) atoms in THFA serve as dual solvation sites, enhancing the desolvation kinetics of [Zn(H2O)6]2+ and improving the deposition dynamics of Zn2+ ions. As a result, even trace amounts of THFA significantly suppress adverse reactions and the formation of Zn dendrites, enabling highly reversible Zn metal anodes for ultralong-life AZIBs. Specifically, a Zn-based symmetric cell containing 2 % THFA achieves an ultralong cycle life of 8,800 h at 0.5 mA cm-2/0.5 mAh cm-2, while a Zn//VO2 full cell containing 2 % THFA maintains a remarkable 80.03 % capacity retention rate at 5 A g-1 over 2,000 cycles. This study presents a practical strategy to develop dendrite-free, cost-effective, and highly efficient aqueous energy storage systems by leveraging alcohol ether compounds with dual-site hydrogen bonding capabilities.

WRAD core perturbation impairs DNA replication fidelity promoting immunoediting in pancreatic cancer.

It is unclear how cells counteract the potentially harmful effects of uncoordinated DNA replication in the context of oncogenic stress. Here, we identify the WRAD (WDR5/RBBP5/ASH2L/DPY30) core as a modulator of DNA replication in pancreatic ductal adenocarcinoma (PDAC) models. Molecular analyses demonstrated that the WRAD core interacts with the replisome complex, with disruption of DPY30 resulting in DNA re-replication, DNA damage, and chromosomal instability (CIN) without affecting cancer cell proliferation. Consequently, in immunocompetent models, DPY30 loss induced T cell infiltration and immune-mediated clearance of highly proliferating cancer cells with complex karyotypes, thus improving anti-tumor efficacy upon anti-PD-1 treatment. In PDAC patients, DPY30 expression was associated with high tumor grade, worse prognosis, and limited response to immune checkpoint blockade. Together, our findings indicate that the WRAD core sustains genome stability and suggest that low intratumor DPY30 levels may identify PDAC patients who will benefit from immune checkpoint inhibitors.

A Patient-Specific 3D Printed Lingual Nerve Protector in Third Molar Extraction.

We present a novel, patient-specific 3D-printed lingual nerve protector designed to minimize the risk of nerve injury during mandibular third molar extraction, a common cause of lingual nerve damage. Lingual nerve injuries, often resulting from trauma, dental procedures, or maxillofacial surgeries, lead to significant functional impairments. Using computed tomography (CT) data, the custom protector is fabricated through 3D printing with a self-retaining structure to shield the lingual mucosa and nerve. The device effectively separates the lingual nerve from the surgical field without requiring retraction of the lingual flap, thereby reducing the risk of nerve injury and enhancing the safety and ease of the procedure.

Concordant and discordant breast density patterns by different approaches for assessing breast density and breast cancer risk.

PURPOSE: To examine the discrepancy in breast density assessments by radiologists, LIBRA software, and AI algorithm and their association with breast cancer risk. METHODS: Among 74,610 Korean women aged ≥ 34 years, who underwent screening mammography, density estimates obtained from both LIBRA and the AI algorithm were compared to radiologists using BI-RADS density categories (A-D, designating C and D as dense breasts). The breast cancer risks were compared according to concordant or discordant dense breasts identified by radiologists, LIBRA, and AI. Cox-proportional hazards models were used to determine adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)]. RESULTS: During a median follow-up of 9.9 years, 479 breast cancer cases developed. Compared to the reference non-dense breast group, the aHRs (95% CIs) for breast cancer were 2.37 (1.68-3.36) for radiologist-classified dense breasts, 1.30 (1.05-1.62) for LIBRA, and 2.55 (1.84-3.56) for AI. For different combinations of breast density assessment, aHRs (95% CI) for breast cancer were 2.40 (1.69-3.41) for radiologist-dense/LIBRA-non-dense, 11.99 (1.64-87.62) for radiologist-non-dense/LIBRA-dense, and 2.99 (1.99-4.50) for both dense breasts, compared to concordant non-dense breasts. Similar trends were observed with radiologists/AI classification: the aHRs (95% CI) were 1.79 (1.02-3.12) for radiologist-dense/AI-non-dense, 2.43 (1.24-4.78) for radiologist-non-dense/AI-dense, and 3.23 (2.15-4.86) for both dense breasts. CONCLUSION: The risk of breast cancer was highest in concordant dense breasts. Discordant dense breast cases also had a significantly higher risk of breast cancer, especially when identified as dense by either AI or LIBRA, but not radiologists, compared to concordant non-dense breast cases.

Comparison of bilateral implantation of monofocal intraocular lenses with enhanced intermediate function targeting with - 2.00 D and emmetropia in moderate to high myopic Asian patients.

BACKGROUND: To investigate the outcomes of bilateral implantation of enhanced monofocal intraocular lenses (IOLs, ICB00) with a - 2.00 diopter (D) target in patients with moderate to high myopia and to compare the clinical outcomes of a - 2.00 D binocular target with an emmetropia target in patients who underwent cataract surgery. METHODS: In this retrospective study, we reviewed the medical records of patients who underwent uncomplicated phacoemulsification with ICB00 IOL implantation. Emmetropia (Group 1) and - 2.00 D (Group 2) were targeted in 60 and 20 eyes of 30 and 10 patients, respectively. Three months after surgery, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), and uncorrected near visual acuity (UNVA) were measured. Defocus curves were measured under the photopic condition by intervals of 0.50 D from + 0.50 D to - 4.00 D. RESULTS: The postoperative binocular logMAR UDVA, UIVA, and UNVA were 0.01 ± 0.03, 0.08 ± 0.11, and 0.33 ± 0.15 in Group 1 and 0.31 ± 0.13, 0.04 ± 0.05, and 0.11 ± 0.07 in Group 2, respectively. Group 2 showed a significantly superior postoperative binocular UNVA (P = 0.027) and inferior binocular UDVA (P = 0.003) than Group 1. Binocular UIVA and CDVA did not significantly differ between the groups although UIVA was better in Group 2 than in Group 1. Near glasses were needed by 66% of Group 1 and 0% of Group 2. CONCLUSIONS: Bilateral implantation of ICB00 IOL with - 2.00 D of residual myopia is suitable for patients with moderate to high myopia to improve UDVA, UIVA, and UNVA.

Therapeutic Effect of Padina arborescens Extract on a Cell System Model for Parkinson's Disease.

Leucine-rich repeat kinase 2 (LRRK2) and α-synuclein are involved in the pathogenesis of Parkinson's disease. The activity of LRRK2 in microglial cells is associated with neuroinflammation, and LRRK2 inhibitors are crucial for alleviating this neuroinflammatory response. α-synuclein contributes to oxidative stress in the dopaminergic neuron and neuroinflammation through Toll-like receptors in microglia. In this study, we investigated the effect of the marine alga Padina arborescens on neuroinflammation by examining LRRK2 activation and the aggregation of α-synuclein. P. arborescens extract inhibits LRRK2 activity in vitro and decreases lipopolysaccharide (LPS)-induced LRRK2 upregulation in BV2, a mouse microglial cell line. Treatment with P. arborescens extract decreased tumor necrosis factor-α (TNF-α) gene expression by LPS through LRRK2 inhibition in BV2. It also attenuated TNF-α gene expression, inducible nitric oxide synthase, and the release of TNF-α and cellular nitric oxide in rat primary microglia. Furthermore, P. arborescens extract prevented rotenone (RTN)-induced oxidative stress in primary rat astrocytes and inhibited α-synuclein fibrilization in an in vitro assay using recombinant α-synuclein and in the differentiated human dopaminergic neuronal cell line SH-SY5Y (dSH). The extract increased lysosomal activity in dSH cells. In addition, P. arborescens extract slightly prolonged the lifespan of Caenorhabditis elegans, which was reduced by RTN treatment.

Serum glucose-potassium ratio predicts inhospital mortality in patients admitted to coronary care unit

SUMMARY OBJECTIVE: The aim of our study was to determine the role of serum glucose-potassium ratio in predicting inhospital mortality in coronary care unit patients. METHODS: This study used data from the MORtality in CORonary Care Units in Turkey study, a national, observational, multicenter study that included all patients admitted to coronary care units between September 1, 2022, and September 30, 2022. Statistical analyses assessed the independent predictors of mortality. Two models were created. Model 1 included age, history of heart failure, chronic kidney disease, hypertension, diabetes mellitus, and coronary artery disease. Model 2 included glucose-potassium ratio in addition to these variables. Multivariate regression and receiver operating characteristic analysis were performed to compare Model 1 and Model 2 to identify if the glucose-potassium ratio is an independent predictor of inhospital mortality. RESULTS: In a study of 3,157 patients, the mortality rate was 4.3% (n=137). Age (p=0.002), female gender (p=0.004), mean blood pressure (p<0.001), serum creatinine (p<0.001), C-reactive protein (p=0.002), white blood cell (p=0.002), and glucose-potassium ratio (p<0.001) were identified as independent predictors of mortality through multivariate regression analysis. The receiver operating characteristic analysis indicated that Model 2 had a statistically higher area under the curve than Model 1 (area under the curve 0.842 vs area under the curve 0.835; p<0.001). A statistically significant correlation was found between the inhospital mortality and glucose-potassium ratio (OR 1.015, 95%CI 1.006-1.024, p<0.001). CONCLUSION: Our study showed that the glucose-potassium ratio may be a significant predictor of inhospital mortality in coronary care unit patients.

NSGS mice humanized with cord blood mononuclear cells show sustained and functional myeloid-lymphoid representation with limited graft-versus-host disease.

Humanized immunodeficient mice serve as critical models for investigating the functional interplay between transplanted human cells and a pre-reconstituted human immune system. These models facilitate the study of molecular and cellular pathogenic mechanisms and enable the evaluation of the efficacy and toxicity of immunotherapies, thereby accelerating their preclinical and clinical development. Current strategies rely on inefficient, long-term/delayed hematopoietic reconstitution by CD34+ hematopoietic progenitors or short-term reconstitution with peripheral blood mononuclear cells (PB-MNCs) associated with high rates of graft-versus-host disease (GvHD) and an inefficient representation of immune cell populations. Here, we hypothesized that immunologically naïve cord blood mononuclear cells (CB-MNCs) could serve as a superior alternative, providing long-lasting and functionally effective immune reconstitution. We conducted a comprehensive comparison between the non-obese diabetic (NOD).Cg-Prkdc∧ˆscid-IL2rg∧ˆtm1Wjl/SzJ (NSG) and NSG-Tg(CMV-IL3,CSF2,KITLG)∧ˆ1Eav/MloySzJ (NSGS) immunodeficient mouse models following humanization with either PB-MNCs or CB-MNCs. We assessed the engraftment dynamics of various human immune cells over time and monitored the development of GvHD in both models. For the most promising model, we extensively evaluated immune cell functionality in vitro and in vivo using sarcoma and leukemia xenografts. Humanizing NSGS mice with CB-MNCs results in a rapid, robust, and sustained representation of a diverse range of functional human lymphoid and myeloid cell populations while minimizing GvHD incidence. In this model, human immune cell populations significantly impair the growth and engraftment of sarcoma and B-cell acute lymphoblastic leukemia cells, with a significant inverse correlation between immune cell levels and tumor growth. This study establishes a fast, efficient, and reliable in vivo platform for various applications in cancer immunotherapy, particularly for exploring the complex interactions between cancer cells, immune cells, and the tumor microenvironment in vivo, prior to clinical development.

Resilience Gap in Gastrointestinal Endoscopy Activity during the COVID-19 Pandemic in South Korea.

This study assessed the impact of distancing measures during the COVID-19 pandemic on cancer diagnostic activities, including gastrointestinal endoscopy (GIE). It analyzed GIE volumes from 2020 to 2022 in comparison to 2018-2019, considering variations in resilience linked to socioeconomic status (SES). The analysis utilized data from the Korean Health Insurance Review and Assessment Services database, covering the entire population and medical facilities. Diagnostic GIE rates (2018-2022) in Gwangju Metropolitan City and Jeonnam province were examined, comparing age-standardized rates (ASRs) by area, gender, and SES. The results indicated a decline in ASRs for colonoscopy and endoscopic gastroduodenoscopy (EGD) in 2020 compared to 2018-2019, followed by an increase in 2021-2022, except for EGD in the medical aid population. SES based and rural-urban disparities were evident in the recovery of GIE rates. The findings suggest that equity-focused strategies are needed to ensure equitable healthcare access among different socioeconomic groups after pandemic.

A noninvasive method of diagnosing membranous nephropathy using exosomes derived from urine.

Background: Membranous nephropathy (MN) is a specific autoimmune disease affecting kidneys. It is characterized by the accumulation of immune complexes in the glomerular basement membrane. Renal biopsy is currently the standard procedure to confirm the diagnosis, although the presence of autoantibodies against the phospholipase A2 receptor (PLA2R) can also help diagnose. In this study, we aimed to investigate the potential of urinary exosomes as noninvasive markers for diagnosing MN. Methods: Exosomes were extracted from urine samples of five patients with MN and four healthy controls. The concentration of PLA2R was measured in both urine and isolated exosomes using enzyme-linked immunosorbent assay techniques. The measurements were adjusted based on the urine creatinine (UCr) level of each participant. Results: The levels of PLA2R/UCr were investigated in urine and urine-derived exosomes from patients and controls. Results of the analysis revealed significantly higher expression of PLA2R/UCr in patients compared to the control group (p < 0.05). Furthermore, the expression level of PLA2R/UCr was higher in urine-derived exosomes than in urine samples. Additionally, a positive correlation was observed between the expression levels of PLA2R/UCr and the urine protein-to-creatinine ratio, with urine-derived exosomes exhibiting a stronger correlation than urine samples. Conclusion: Studies have indicated that measuring exosomal PLA2R/UCr levels in urine could be a noninvasive method for diagnosing MN. Using urine-derived exosomes could also reduce the burden of performing a biopsy on patients and facilitate follow-up treatment, such as monitoring for future recurrence.

Conventional machine learning-based prediction models did not outperform the International IgA Nephropathy Prediction Tool.

Background: Immunoglobulin A nephropathy (IgAN) is a major cause of end-stage kidney disease (ESKD). The International IgA Nephropathy Prediction Tool (IIgAN-PT) predicts IgAN prognosis, but improvement in the prediction performance using machine learning (ML)-based methods is needed. Methods: We analyzed 4,425 biopsy-confirmed patients with IgAN and ≥6 months of follow-up from nine tertiary university hospitals in Korea. The study population was divided into development and validation cohorts. Using the collected 87 clinicodemographic and pathological variables, ML-based prediction models for ESKD or estimated glomerular filtration rate were constructed: 1) the conventional CatBoost model, 2) the optimized CatBoost model with Cox proportional hazards, 3) the deep Cox proportional hazards model, and 4) the deep Cox mixture model. The area under the curve (AUC) and calibration plots were used to investigate the discriminative and calibration performance of the models, which were then compared with those of the IIgAN-PT full model. Results: The full model showed excellent performance (AUC [95% confidence interval] for 5-year outcome, 0.896 [0.8530.940]), with acceptable calibration results. The ML-based models showed good performance in predicting adverse kidney outcomes and revealed acceptable discrimination performance in the external validation (AUC [95% confidence interval] for the 5-year outcome: 1) 0.829 [0.791-0.866]; 2) 0.847 [0.804-0.890]; 3) 0.823 [0.784-0.862]; and 4) 0.832 [0.794-0.870]), although they underestimated the external validation cohort risks. With the validation data, the overall performance of the IIgAN-PT was non-inferior to that of the ML-based model. Conclusions: Our ML-based models showed good performance in predicting adverse kidney outcomes in patients with IgAN but they did not outperform the IIgAN-PT.

Targeting the Hippo pathway in Schwann cells ameliorates peripheral nerve degeneration via a polypharmacological mechanism.

Peripheral neuropathies (PNs) are common diseases in elderly individuals characterized by Schwann cell (SC) dysfunction and irreversible Wallerian degeneration (WD). Although the molecular mechanisms of PN onset and progression have been widely studied, therapeutic opportunities remain limited. In this study, we investigated the pharmacological inhibition of Mammalian Ste20-like kinase 1/2 (MST1/2) by using its chemical inhibitor, XMU-MP-1 (XMU), against WD. XMU treatment suppressed the proliferation, dedifferentiation, and demyelination of SCs in models of WD in vitro, in vivo, and ex vivo. As a downstream mediator of canonical and noncanonical Hippo/MST1 pathway activation, the mature microRNA (miRNA) let-7b and its binding partners quaking homolog (QKI)/nucleolin (NCL) modulated miRNA-mediated silencing of genes involved in protein transport. Hence, direct phosphorylation of QKI and NCL by MST1 might be critical for WD onset and pathogenesis. Moreover, p38α/mitogen-activated protein kinase 14 (p38α) showed a strong affinity for XMU, and therefore, it may be an alternative XMU target for controlling WD in SCs. Taken together, our findings provide new insights into the Hippo/MST pathway function in PNs and suggest that XMU is a novel multitargeted therapeutic for elderly individuals with PNs.

Faith, Meaning, and Quality of Life: Unveiling the Spirituality of Muslim Patients with Advanced Cancer Undergoing Active Treatment in the Gaza Strip, Palestine.

OBJECTIVES: This study aimed to identify the level of spirituality, faith and meaning, and quality of life (QOL) among Muslim advanced cancer patients undergoing active treatment and to enhance the understanding of the relationships among clinical and socio-demographic factors, spirituality, and QOL of patients in the Gaza Strip. METHODS: A secondary analysis was conducted on a convenience sample of 298 advanced cancer patients. The Arabic versions of the Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) and the Functional Assessment of Cancer Therapy-General (FACT-G) were used for data collection. Descriptive statistics and generalized linear regression were utilized for data analysis, performed using SPSS 25.0. RESULTS: Participants reported high spirituality well-being scores (Mean = 31.25, SD = 6.25) and relatively high scores on the subscales of meaning/peace (Mean = 19.15, SD = 4.11) and faith (Mean = 12.03, SD = 3.50). Most patients indicated that their faith and spiritual beliefs increased due to their illness. Furthermore, a significant positive relationship was found between spirituality (including its subscales of faith and meaning in life) and QOL. Despite the generally high level of spirituality, special attention should be paid to patients with lung, bladder, and thyroid cancer, lower education levels, and higher cancer grades. CONCLUSIONS: The Gazan Muslim patients with advanced cancer exhibit high levels of spirituality and faith. We acknowledged that spiritual well-being is a protective factor for QOL. The strong positive correlation between spirituality and QOL emphasizes the need to integrate spiritual care into cancer care. IMPLICATIONS FOR NURSING PRACTICE: It is imperative to incorporate spirituality into health practice and the daily routines of cancer treatment for patients whose spirituality is an important aspect of their identities. The incorporation of spirituality can contribute to the improvement of the quality of patients' life and quality of cancer care.

Sensitivity, Specificity, and Cost-Benefit Effect Between Primary Human Papillomavirus Testing, Primary Liquid-Based Cytology, and Co-Testing Algorithms for Cervical Lesions.

BACKGROUND: Cytology has long been a major screening method for cervical cancer prevention. Human papillomavirus (HPV) testing has recently been introduced for cervical cancer screening, and HPV tests become a major screening method in some countries. To seek the optimal strategy considering the cost-effectiveness for cervical cancer screening, we compared the performance of primary LBC, primary HPV test, and LBC plus HPV co-test in real practice. METHODS: From March 2016 to June 2018, 3742 patients were included in this study. Liquid-based cytology (LBC), HPV test, and histopathological assessment were performed in 3727, 1063, and 508 cases, respectively. The sensitivity, specificity, and cost-benefit effects of primary HPV, primary LBC, and co-test algorithms were simulated for 317 cases with LBC, HPV, and histopathological results. RESULTS: On the LBC, 13.0% of the cases were diagnosed with atypical squamous cells of undetermined significance or higher grade lesions. In the HPV test, high-risk HPV was found in 43.5%, and 11.9% was positive for HPV type 16 or 18. Among the three simulated algorithms, the co-test demonstrated the best sensitivity (97.5%) and the lowest specificity (50.3%). The primary LBC demonstrated the best specificity (53.5%) and a slightly better sensitivity, compare with the primary HPV (95.1% vs. 93.8%). Using the primary LBC algorithm, 82.0% can be determined without additional HPV test, whereas 50.1% could be determined without additional LBC using the primary HPV algorithm. CONCLUSIONS: The primary LBC algorithm for uterine cervical cancer (UCC) screening is comparable to the primary HPV algorithm and has the best cost-benefit effect among the three algorithms.

PEDF-Enriched Extracellular Vesicle for Vessel Normalization to Potentiate Immune Checkpoint Blockade Therapy.

The abnormal tumor vasculature acts as the physical and functional barrier to the infiltration and activity of effector T cells, leading to the low response rate of immune checkpoint inhibitors (ICIs). Herein, antiangiogenic extracellular vesicles that enable normalization of the tumor-associated vasculature were prepared to potentiate the efficacy of ICIs. Small extracellular vesicles were exploited as the delivery platform to protect the antiangiogenic protein, pigment epithelium-derived factor (PEDF), from proteolytic degradation. Along with the physicochemical characteristics of the PEDF-enriched extracellular vesicles (P-EVs), their inhibitory effects on migration, proliferation, and tube formation of endothelial cells were investigated in vitro. In tumor-bearing mice, it was confirmed that, compared to bare PEDFs, P-EVs efficiently reduced vessel leakiness, improved blood perfusion, and attenuated hypoxia. Consequently, when combined with anti-PD-1 antibodies, P-EVs remarkably augmented the antitumor immunity, as evidenced by increased infiltration of CD8+ T cells and reduced regulatory T cells. These results suggest that P-EVs are promising therapeutics for tumors refractory to ICIs.

MG53's non-physiologic interaction with insulin receptor: lack of effect on insulin-stimulated Akt phosphorylation in muscle, heart and liver tissues.

Rationale: MG53's known function in facilitating tissue repair and anti-inflammation has broad applications to regenerative medicine. There is controversy regarding MG53's role in the development of type 2 diabetes mellitus. Objective: This study aims to address this controversy - whether MG53's myokine function contributes to inhibition of insulin signaling in muscle, heart, and liver tissues. Study design: We determined the binding affinity of the recombinant human MG53 (rhMG53) to the insulin receptor extracellular domain (IR-ECD) and found low affinity of interaction with Kd (>480 nM). Using cultured C2C12 myotubes and HepG2 cells, we found no effect of rhMG53 on insulin-stimulated Akt phosphorylation (p-Akt). We performed in vivo assay with C57BL/6J mice subjected to insulin stimulation (1 U/kg, intraperitoneal injection) and observed no effect of rhMG53 on insulin-stimulated p-Akt in muscle, heart and liver tissues. Conclusion: Overall, our data suggest that rhMG53 can bind to the IR-ECD, however has a low likelihood of a physiologic role, as the Kd for binding is ~10,000 higher than the physiologic level of MG53 present in the serum of rodents and humans (~10 pM). Our findings question the notion proposed by Xiao and colleagues - whether targeting circulating MG53 opens a new therapeutic avenue for type 2 diabetes mellitus and its complications.

Presumed solitary ocular lymphoma of large B-cell origin with Mott cell change in a dog.

A 4-year-old female Maltese dog was referred to our veterinary hospital with uveitis and conjunctivitis of the right eye. An ophthalmological evaluation revealed an intraocular mass that appeared to originate from the anterior uvea. Metastasis and regional invasion were not detected with CT examination. Enucleation of the right eye was recommended; however, the owner declined treatment. Six months later, the dog was re-presented with a right facial mass. At presentation, superficial lymph node enlargement was not appreciated, and no apparent alterations were noted on blood analysis or urinalysis. Computed tomography revealed an intraocular mass that invaded the surrounding tissues, including the frontal sinus. Presumed solitary ocular lymphoma with a large B-cell phenotype and Mott cell change was diagnosed via histopathological and immunohistochemical examination of a biopsy of the lesion. As the mass was too large for complete excision, neoadjuvant chemotherapy was administered. Complete remission was achieved using the L-COAP protocol and successful exenteration of the right eye. However, the dog was returned with enlargement of the right retropharyngeal lymph nodes. To the best of our knowledge, this is the first case report of presumed solitary ocular lymphoma with a large B-cell phenotype displaying Mott cell change in a dog. Key clinical message: This is the first reported case of a presumed solitary ocular lymphoma with a large B-cell phenotype and Mott cell change. Although systemic involvement was observed 6 mo after the initial visit, neoadjuvant chemotherapy and exenteration were effective.

Lymphome oculaire solitaire présumé d'origine à grandes cellules B avec modification des cellules de Mott chez un chienUne chienne maltaise de 4 ans a été envoyée à notre hôpital vétérinaire avec une uvéite et une conjonctivite de l'œil droit. Une évaluation ophtalmologique a révélé une masse intraoculaire qui semblait provenir de l'uvée antérieure. Aucune métastase ni invasion régionale n'ont été détectées par examen CT. Une énucléation de l'œil droit a été recommandée; cependant, le propriétaire a refusé le traitement. Six mois plus tard, le chien a été présenté à nouveau avec une masse faciale droite. À la présentation, l'augmentation de taille des ganglions lymphatiques superficiels n'a pas été réalisée, et aucune modification apparente n'a été notée sur l'analyse sanguine ou l'analyse d'urine. La tomodensitométrie a révélé une masse intraoculaire qui a envahi les tissus environnants, y compris le sinus frontal. Un lymphome oculaire solitaire présumé avec un phénotype à grandes cellules B et une modification des cellules de Mott a été diagnostiqué via un examen histopathologique et immunohistochimique d'une biopsie de la lésion. Comme la masse était trop importante pour une exérèse complète, une chimiothérapie néoadjuvante a été administrée. Une rémission complète a été obtenue grâce au protocole L-COAP et à une exentération réussie de l'œil droit. Cependant, le chien a été vu de nouveau avec une hypertrophie des ganglions lymphatiques rétropharyngés droits. À notre connaissance, il s'agit du premier cas rapporté de lymphome oculaire solitaire présumé avec un phénotype à grandes cellules B présentant une modification des cellules de Mott chez un chien.Message clinique clé :Il s'agit du premier cas rapporté de lymphome oculaire solitaire présumé avec un phénotype à grandes cellules B et une modification des cellules de Mott. Bien qu'une atteinte systémique ait été observée 6 mois après la visite initiale, la chimiothérapie néoadjuvante et l'exentération ont été efficaces.(Traduit par Dr Serge Messier).

A hybrid case of eosinophilic folliculitis and eosinophilic cellulitis associated with hypereosinophilic syndrome.

Eosinophilic cellulitis or Wells syndrome encompasses distinct histopathological features but can also be associated with eosinophilic related conditions like hyper eosinophilic syndrome (HES) or eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome). We report a case of a Turkish 41-year-old female who presented in clinic with pruritus and tenderness on her chest and breasts, having received several courses of antibiotics for recurrent abscess formation. A year before she had been diagnosed with HES with multiorgan involvement that included biopsy proven eosinophilic folliculitis, and prompted further investigation including bone marrow aspiration that revealed T cell clonality. Biopsy of her rash revealed eosinophilic infiltration of the dermis with flame figures. Ongoing respiratory symptoms and a history of childhood asthma were suggestive of EGPA. This case highlights important associations that should be considered in the investigation of Wells syndrome.